The mineral component of bone, dentin and calcified parts of avian tendon, hydroxyapatite (HAP), has non-stoichiometric composition (idealized as Ca₁₀(PO₄)₆(OH)₂), plate-like morphology and nanometer size. This unique crystal morphology contributes to the physico-chemical and biochemical properties of bone. Thus, understanding the mechanism for the controlled growth of plate-like HAP nanocrystals is significant in the study of bone biomineralization. Previous studies have shown that acidic non-collagenous proteins (ANCPs), which are enriched in the residues of acidic amino acids, may play an important role in HAP crystal growth modulation. In this study, glutamic acid (Glu) and phosphoserine (Ser-OPO₃) were used as model compounds to modify the synthesis of HAP nanocrystals. To identify the mechanisms of amino acids as regulators, X-ray diffraction (XRD), transmission electron microscopy (TEM) and solid state nuclear magnetic resonance (ssNMR) were used. The crystals obtained in the inorganic controls were needle-like, while crystals synthesized in the presence of the amino acids presented a plate-like morphology. The plate-like crystals had a preferred crystal orientation on (300) face, which was lacking in the inorganically grown crystals, indicating preferential adsorption and suppression of growth in specific crystal directions. Ser-OPO₃ was more efficient than Glu in modulating HAP nucleation and crystal growth. Furthermore, NMR revealed interactions between the charged side chain groups in amino acids and the crystal surfaces. These results were successfully explained through our MD simulations for the free energy calculation of amino acid binding on HAP crystal faces. The present study revealed that amino acids may act as effective regulators of HAP morphology without the need to invoke large NCPs in bone biomineralization and in designing bioinspired materials for orthopaedic and dental applications.

The self-assembly of lipid bilayer membranes to enclose functional biomolecules, thus defining a “protocell,” was a seminal moment in the emergence of life on Earth and likely occurred at the micro-environment of the mineral-water interface. Mineral-lipid interactions are also relevant in biomedical, industrial and technological processes. Yet, no structure-activity relationships (SARs) have been identified to predict lipid self-assembly at mineral surfaces. Here we examined the influence of minerals on the self-assembly and survival of vesicles composed of single chain amphiphiles as model protocell membranes. The apparent critical vesicle concentration (CVC) increased in the presence of positively-charged nanoparticulate minerals at high loadings (mg/mL) suggesting unfavorable membrane self-assembly in such situations. Above the CVC, initial vesicle formation rates were faster in the presence of minerals. Rates were correlated with the mineral’s isoelectric point (IEP) and reactive surface area. The IEP depends on the crystal structure, chemical composition and surface hydration. Thus, membrane self-assembly showed rational dependence on fundamental mineral properties. Once formed, membrane permeability (integrity) was unaffected by minerals. Suggesting that, protocells could have survived on rock surfaces. These SARs may help predict the formation and survival of protocell membranes on early Earth and other rocky planets, and amphiphile-mineral interactions in diverse other phenomena.